SUMMARY OF PROPOSED WORK: An assay of increased capillary permeability in experimental diabetes is proposed which involves the ultrastructural localization of electron dense markers. Diabetes will be induced in rats chiefly by means of an intraperitoneal injection of alloxan. Previous studies of similar diabetic animals have revealed increased penetration of horseradish peroxidase in the area of postrema and skeletal muscle, and more rapid equilibration of I-125 PVP between blood and tissue. This study is intended to characterize this vascular leak more completely by applying quantitative methods of assay for peroxidase activity. We hope to determine whether exercising muscles equilibrate differently than muscles and also whether there is any difference in permeability between resting muscles that are largely composed of differing fiber types.